Late deaths among five-year survivors of childhood cancer. A population-based study in Piedmont Region, Italy

Background and objectives. The aim of this study was to analyze late mortality among 5-year survivors of childhood cancer, in Piedmont (Italy), in terms of risk factors and causes of death. Design and Methods. From 1967 to 1999, the Childhood Cancer Registry of Piedmont recorded 3164 incident cases. Patients identified only by a death certificate (n=59), lost to follow-up (n=32), alive with a period of observation shorter than 5 years at the end of follow-up (n=65) and records corresponding to a second malignant tumor during childhood (n=9) were excluded from the analyses. Results. Within 5 years after diagnosis, 1301 children died, and among the 1698 5-year survivors, 144 children subsequently died. Among 5-year survivors, cumulative mortality percentages increased from 5.1% (95% CI 4.0-6.2) at 10 years after diagnosis to 16.0% (12.2-19.8) at 35 years. Period of diagnosis (p=0.006), age at diagnosis (p=0.002), and tumor type (p=0.003) were associated with late mortality. Most deaths were related to cancer recurrence (62.2%) and treatment-related sequelae (22.4%), including second malignant neoplasms, cardiac diseases and other late effects. Compared to the general population, children included in this study had a 9-fold increased risk of overall mortality, and experienced an absolute excess of 4.4 deaths per 1000 person-years. Interpretation and Conclusions. Among 5-year survivors, patients treated more recently (after 1979) had a statistically significant lower risk of late death than those treated earlier. However, long-term survivors still experienced higher mortality rates than those in the general population, and recurrence or progression of the primary tumor was the first cause of death.